RESUMO
BACKGROUND: Breast cancer is the most common malignant tumor, and metastasis remains the major cause of poor prognosis. Glucose metabolic reprogramming is one of the prominent hallmarks in cancer, providing nutrients and energy to support dramatically elevated tumor growth and metastasis. Nevertheless, the potential mechanistic links between glycolysis and breast cancer progression have not been thoroughly elucidated. METHODS: RNA-seq analysis was used to identify glucose metabolism-related circRNAs. The expression of circSIPA1L3 in breast cancer tissues and serum was examined by qRT-PCR, and further assessed its diagnostic value. We also evaluated the prognostic potential of circSIPA1L3 by analyzing a cohort of 238 breast cancer patients. Gain- and loss-of-function experiments, transcriptomic analysis, and molecular biology experiments were conducted to explore the biological function and regulatory mechanism of circSIPA1L3. RESULTS: Using RNA-seq analysis, circSIPA1L3 was identified as the critical mediator responsible for metabolic adaption upon energy stress. Gain- and loss-of-function experiments revealed that circSIPA1L3 exerted a stimulative effect on breast cancer progression and glycolysis, which could also be transported by exosomes and facilitated malignant behaviors among breast cancer cells. Significantly, the elevated lactate secretion caused by circSIPA1L3-mediated glycolysis enhancement promoted the recruitment of tumor associated macrophage and their tumor-promoting roles. Mechanistically, EIF4A3 induced the cyclization and cytoplasmic export of circSIPA1L3, which inhibited ubiquitin-mediated IGF2BP3 degradation through enhancing the UPS7-IGF2BP3 interaction. Furthermore, circSIPA1L3 increased mRNA stability of the lactate export carrier SLC16A1 and the glucose intake enhancer RAB11A through either strengthening their interaction with IGF2BP3 or sponging miR-665, leading to enhanced glycolytic metabolism. Clinically, elevated circSIPA1L3 expression indicated unfavorable prognosis base on the cohort of 238 breast cancer patients. Moreover, circSIPA1L3 was highly expressed in the serum of breast cancer patients and exhibited high diagnostic value for breast cancer patients. CONCLUSIONS: Our study highlights the oncogenic role of circSIPA1L3 through mediating glucose metabolism, which might serve as a promising diagnostic and prognostic biomarker and potential therapeutic target for breast cancer.
Assuntos
Progressão da Doença , Exossomos , Regulação Neoplásica da Expressão Gênica , Glucose , RNA Circular , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Exossomos/metabolismo , RNA Circular/genética , Glucose/metabolismo , Camundongos , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/genética , Animais , Prognóstico , Glicólise , Linhagem Celular Tumoral , Biomarcadores Tumorais/metabolismo , Proliferação de Células , Reprogramação Metabólica , Proteínas de Membrana , Peptídeos e Proteínas de Sinalização IntracelularRESUMO
IMPORTANCE: Several coronaviruses (CoVs) have been detected in domesticated, farmed, and wild meso-carnivores, causing a wide range of diseases and infecting diverse species, highlighting their important but understudied role in the epidemiology of these viruses. Assessing the viral diversity hosted in wildlife species is essential to understand their significance in the cross-species transmission of CoVs. Our focus here was on CoV discovery in meso-carnivores in the Northeast United States as a potential "hotspot" area with high density of humans and urban wildlife. This study identifies novel alphacoronaviruses circulating in multiple free-ranging wild and domestic species in this area and explores their potential epidemiological importance based on regions of the Spike gene, which are relevant for virus-host interactions.
Assuntos
Alphacoronavirus , Carnívoros , Fezes , Saliva , Animais , Humanos , Alphacoronavirus/classificação , Alphacoronavirus/genética , Alphacoronavirus/isolamento & purificação , Animais Domésticos/virologia , Animais Selvagens/virologia , Carnívoros/virologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/veterinária , Fezes/virologia , Interações entre Hospedeiro e Microrganismos , New England/epidemiologia , Saliva/virologia , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismo , Zoonoses Virais/transmissão , Zoonoses Virais/virologiaRESUMO
Straw incorporation holds significant promise for enhancing soil fertility and mitigating air pollution stemming from straw burning. However, this practice concurrently elevates the production and emission of methane (CH4) from paddy ecosystems. Despite its environmental impact, the precise mechanisms behind the heightened CH4 production resulting from long-term straw incorporation remain elusive. In a 32-year field experiment featuring three fertilization treatments (CFS-chemical fertilizer with wheat straw, CF-chemical fertilizer, and CK-unamended), we investigated the impact of abiotic (soil physicochemical properties) and biotic (methanogenic abundance, diversity, and community composition) factors on CH4 production in paddy fields. Results revealed a significantly higher CH4 production potential under CFS treatment compared to CF and CK treatments. The partial least squares path model revealed that soil physicochemical properties (path coefficient = 0.61), methanogenic diversity (path coefficient = -0.43), and methanogenic abundance (path coefficient = 0.29) collectively determined CH4 production potential, explaining 77% of the variance. Enhanced soil organic carbon content and water content, resulting from straw incorporation, emerged as pivotal factors positively correlated with CH4 production potential. Under CFS treatment, lower Shannon index of methanogens, compared to CF and CK treatments, was attributed to increased Methanosarcina. Notably, the Shannon index and relative abundance of Methanosarcina exhibited negative and positive correlations with CH4 production potential, respectively. Methanogenic abundance, bolstered by straw incorporation, significantly amplified overall potential. This comprehensive analysis underscores the joint influence of abiotic and biotic factors in regulating CH4 production potential during multi-decadal straw incorporation.
Assuntos
Metano , Microbiologia do Solo , Solo , Metano/biossíntese , Metano/metabolismo , Solo/química , Oryza , Agricultura/métodos , Fertilizantes/análiseRESUMO
BACKGROUND: Triple-negative breast cancer (TNBC) is a subtype of breast cancer with higher aggressiveness and poorer outcomes. Recently, long non-coding RNAs (lncRNAs) have become the crucial gene regulators in the progression of human cancers. However, the function and underlying mechanisms of lncRNAs in TNBC remains unclear. METHODS: Based on public databases and bioinformatics analyses, the low expression of lncRNA MIDEAS-AS1 in breast cancer tissues was detected and further validated in a cohort of TNBC tissues. The effects of MIDEAS-AS1 on proliferation, migration, invasion were determined by in vitro and in vivo experiments. RNA pull-down assay and RNA immunoprecipitation (RIP) assay were carried out to reveal the interaction between MIDEAS-AS1 and MATR3. Luciferase reporter assay, Chromatin immunoprecipitation (ChIP) and qRT-PCR were used to evaluate the regulatory effect of MIDEAS-AS1/MATR3 complex on NCALD. RESULTS: LncRNA MIDEAS-AS1 was significantly downregulated in TNBC, which was correlated with poor overall survival (OS) and progression-free survival (PFS) in TNBC patients. MIDEAS-AS1 overexpression remarkably inhibited tumor growth and metastasis in vitro and in vivo. Mechanistically, MIDEAS-AS1 mainly located in the nucleus and interacted with the nuclear protein MATR3. Meanwhile, NCALD was selected as the downstream target, which was transcriptionally regulated by MIDEAS-AS1/MATR3 complex and further inactivated NF-κB signaling pathway. Furthermore, rescue experiment showed that the suppression of cell malignant phenotype caused by MIDEAS-AS1 overexpression could be reversed by inhibition of NCALD. CONCLUSIONS: Collectively, our results demonstrate that MIDEAS-AS1 serves as a tumor-suppressor in TNBC through modulating MATR3/NCALD axis, and MIDEAS-AS1 may function as a prognostic biomarker for TNBC.
Assuntos
MicroRNAs , Neurocalcina , RNA Longo não Codificante , Neoplasias de Mama Triplo Negativas , Humanos , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Neurocalcina/genética , Neurocalcina/metabolismo , Proteínas Associadas à Matriz Nuclear/genética , Proteínas Associadas à Matriz Nuclear/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Proteínas de Ligação a RNA/genética , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologiaRESUMO
The simulation of abrupt atmospheric CO2 increase is a common way to examine the response of soil methanotrophs to future climate change. However, atmosphere is undergoing a gradual CO2 increase, and it is unknown whether the previously reported response of methanotrophs to abrupt CO2 increase can well represent their response to the gradual increase. To improve the understanding of the effect of elevated CO2 (eCO2) on methanotrophs in paddy ecosystems, the methane oxidation potential and communities of methanotrophs were examined via open top chambers under the three following CO2 treatments: an ambient CO2 concentration (AC); an abrupt CO2 increase by 200 ppm above AC (AI); a gradual CO2 increase by 40 ppm each year until 200 ppm above AC (GI). Relative to AC treatment, AI and GI treatments significantly (p < 0.05) increased the methane oxidation rate by 43.8% and 36.7%, respectively, during rice growth period. Furthermore, the abundance of pmoA genes was significantly (p < 0.05) increased by 62.4% and 32.5%, respectively, under AI and GI treatments. However, there were no significant variations in oxidation rate or gene abundance between the two eCO2 treatments. In addition, no obvious change of overall community composition of methanotrophs was observed among treatments, while the proportions of Methylosarcina and Methylocystis significantly (p < 0.05) changed. Taken together, our results indicate similar response of methanotrophs to abrupt and gradual CO2 increase, although the magnitude of response under gradual increase was smaller and the abrupt increase may somewhat overestimate the response.
Assuntos
Ecossistema , Oryza , Dióxido de Carbono , Solo , Oxirredução , Metano , Microbiologia do SoloRESUMO
Fumaric acid production from lignocellulosic materials is an alternative chemicals production system. This work investigated the suitable conditions for hydrolysis of dried distiller's grains with solubles (DDGS). The hydrolytic liquid was subsequently used for the production of fumaric acid. After optimizing the hydrolysis conditions, the most suitable concentration of H2SO4 (2%), hydrolysis temperature (120 °C), hydrolysis time (100min) and solid/liquid ratio (1:10) were obtained. The yield of monosaccharides reached 258 mg/g DDGS and 15.88 g/L glucose, 7.53 g/L xylose and 2.35 g/L arabinose were obtained in unprocessed hydrolytic liquid. The furfural inhibitor in the hydrolytic liquid was also detected and the yield of it was reducing progressively in the pretreatment process. The ferment ability of the hydrolytic liquid from DDGS was tested through the process of fumaric acid production by Rhizopus arrhizus RH 7-13. The unprocessed hydrolytic liquid was not appropriate for the fermentation process. The yield of fumaric acid from the concentrated processed hydrolytic liquid reached 18.93 g/L, which was close to the yield of fermenting 80 g/L glucose. This result indicated that the commonly used carbon resource glucose could to some extent be replaced by processed hydrolytic liquid.
Assuntos
Fumaratos , Rhizopus , Fermentação , XiloseRESUMO
Iron-dependent anaerobic oxidation of methane (iron-AOM) has recently been reported to occur in paddy soils, but its actual role and regulation remain unclear. Here, we confirmed the occurrence of iron-AOM at different layers of paddy soils (0-10 cm, 10-20 cm, and 30-40 cm) across tillering, elongation, flowering, and ripening periods under three long-term fertilizer management schemes (CK-unamended, CF-chemical fertilizer, and CFS-chemical fertilizer with straw). The iron-AOM activity contributed 41 % to total AOM, which was greater than that of nitrite- (32 %) and nitrate-AOM (27 %). The iron-AOM activity varied significantly with soil layers, growth periods and fertilizer types, with layer being the most important variable. Soil moisture content and organic carbon content were most significant influencing factors on the AOM activity, and a Candidatus Methanoperedens ferrireducens-like lineage potentially catalyzed iron-AOM. Our results suggest that iron-AOM has an important potential for mitigating methane emissions from rice paddies.
Assuntos
Agricultura , Fertilizantes , Ferro , Metano , Oryza , Oryza/crescimento & desenvolvimento , Metano/análise , Agricultura/métodos , Solo/química , Oxirredução , Microbiologia do SoloRESUMO
Breast cancer is one of the major malignant tumors among women worldwide. Long noncoding RNAs (lncRNAs) have been documented as significant modulators in the development and progression of various cancers; however, the contribution of lncRNAs to breast cancer remains largely unknown. In this study, we found a novel lncRNA (NONHSAT137675) whose expression was significantly increased in the breast cancer tissues. We named the novel lncRNA as lncRNA PRBC (PABPC1-related lncRNA in breast cancer) and identified it as a key lncRNA associated with breast cancer progression and prognosis. Functional analysis displayed that lncRNA PRBC could promote autophagy and progression of breast cancer. Mechanistically, we verified that lncRNA PRBC physically interacted with PABPC1 through RIP assay, and PABPC1 overexpression could reverse the inhibiting effect of lncRNA PRBC knockdown on the malignant behaviors in breast cancer cells. Knockdown of lncRNA PRBC interfered the translocation of PABPC1 from nucleus to cytoplasm as indicated by western blot and IF assays. Significantly, the cytoplasmic location of PABPC1 was required for the interaction between PABPC1 and AGO2, which could be enhanced by lncRNA PRBC overexpression, leading to strengthened recruitment of mRNA to RNA-induced silencing complex (RISC) and thus reinforcing the inhibition efficiency of miRNAs. In general, lncRNA PRBC played a critical role in malignant progression of breast cancer by inducing the cytoplasmic translocation of PABPC1 to further regulate the function of downstream miRNAs. This study provides novel insight on the molecular mechanism of breast cancer progression, and lncRNA PRBC might be a promising therapeutic target and prognostic predictor for breast cancer.
Assuntos
Neoplasias da Mama , Proteína I de Ligação a Poli(A) , RNA Longo não Codificante , Feminino , Humanos , Autofagia/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Proteína I de Ligação a Poli(A)/genética , Proteína I de Ligação a Poli(A)/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética , Proteínas de Ligação a RNA/genéticaRESUMO
The second-leading cause of death, cancer, poses a significant threat to human life. Innovations in cancer therapies are crucial due to limitations in traditional approaches. Newcastle disease virus (NDV), a nonpathogenic oncolytic virus, exhibits multifunctional anticancer properties by selectively infecting, replicating, and eliminating tumor cells. To enhance NDV's antitumor activity, four oncolytic NDV viruses were developed, incorporating IL24 and/or GM-CSF genes at different gene loci using reverse genetics. In vitro experiments revealed that oncolytic NDV virus augmented the antitumor efficacy of the parental virus rClone30, inhibiting tumor cell proliferation, inducing tumor cell fusion, and promoting apoptosis. Moreover, NDV carrying the IL24 gene inhibited microvessel formation in CAM experiments. Evaluation in a mouse model of liver cancer confirmed the therapeutic efficacy of oncolytic NDV viral therapy. Tumors in mice treated with oncolytic NDV virus significantly decreased in size, accompanied by tumor cell detachment and apoptosis evident in pathological sections. Furthermore, oncolytic NDV virus enhanced T cell and dendritic cell production and substantially improved the survival rate of mice with hepatocellular carcinoma, with rClone30-IL24(P/M) demonstrating significant therapeutic effects. This study establishes a basis for utilizing oncolytic NDV virus as an antitumor agent in clinical practice.
Assuntos
Interleucinas , Vírus da Doença de Newcastle , Terapia Viral Oncolítica , Vírus Oncolíticos , Animais , Vírus da Doença de Newcastle/genética , Vírus da Doença de Newcastle/fisiologia , Terapia Viral Oncolítica/métodos , Vírus Oncolíticos/genética , Vírus Oncolíticos/fisiologia , Humanos , Camundongos , Linhagem Celular Tumoral , Interleucinas/genética , Interleucinas/metabolismo , Neoplasias Hepáticas/terapia , Camundongos Endogâmicos BALB C , Carcinoma Hepatocelular/terapia , Apoptose , Neovascularização Patológica/terapia , Proliferação de Células , Fator Estimulador de Colônias de Granulócitos e Macrófagos/genética , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Células Dendríticas/imunologia , Linfócitos T/imunologiaRESUMO
Organic acids are important consumable materials with a wide range of applications in the food, biopolymer and chemical industries. The global consumer organic acids market is estimated to increase to $36.86 billion by 2026. Conventionally, organic acids are produced from the chemical catalysis process with petrochemicals as raw materials, which posts severe environmental concerns and conflicts with our sustainable development goals. Most of the commonly used organic acids can be produced from various organisms. As a state-of-the-art technology, large-scale fermentative production of important organic acids with genetically-modified microbes has become an alternative to the chemical route to meet the market demand. Despite the fact that bio-based organic acid production from renewable cheap feedstock provides a viable solution, low productivity has impeded their industrial-scale application. With our deeper understanding of strain genetics, physiology and the availability of strain engineering tools, new technologies including synthetic biology, various metabolic engineering strategies, omics-based system biology tools, and high throughput screening methods are gradually established to bridge our knowledge gap. And they were further applied to modify the cellular reaction networks of potential microbial hosts and improve the strain performance, which facilitated the commercialization of consumable organic acids. Here we present the recent advances of metabolic engineering strategies to improve the production of important organic acids including fumaric acid, citric acid, itaconic acid, adipic acid, muconic acid, and we also discuss the current challenges and future perspectives on how we can develop a cost-efficient, green and sustainable process to produce these important chemicals from low-cost feedstocks.
Assuntos
Engenharia Metabólica , Compostos Orgânicos , Engenharia Metabólica/métodos , Fermentação , Ácido CítricoRESUMO
Z-scheme heterojunction-based photocatalysts typically have robust removal efficiencies for water contaminants. Herein, we employed p-type PhC2Cu and n-type UiO-66-NH2 to develop a direct Z-scheme UiO-66-NH2/PhC2Cu photocatalyst with an ultrahigh redox potential for Cr(VI) photoreduction and norfloxacin (NOR) photodegradation. Moreover, UV-vis diffuse reflectance, photoelectrochemical measurements, photoluminescence (PL) spectra and electron spin resonance (ESR) technique revealed that the UiO-66-NH2/PhC2Cu composite boosted light capturing capacities to promote photocatalytic efficiencies. Strikingly, the optimized UiO-66-NH2/PhC2Cu50 wt% rapidly reduced Cr(VI) (96.2%, 15 min) and degraded NOR (97.9%, 60 min) under low-power blue LED light. In addition, the UiO-66-NH2/PhC2Cu photocatalyst also exhibited favorable mineralization capacity (78.4%, 120 min). Benefitting from the enhanced interfacial electron transfer and ultrahigh redox potential of the Z-scheme heterojunction, the UiO-66-NH2/PhC2Cu photocatalyst greatly enhanced the separation efficacies of photogenerated carriers. This resulting abundance of active species (e.g., e-, h+, O2â¢-, and â¢OH) were generated to photo-reduce Cr(VI) and photo-oxidize NOR. Base on the identified intermediates, four degradation pathways of NOR were proposed. Finally, the Z-scheme mechanism were systematically confirmed through X-ray photoelectron spectroscopy (XPS), ESR, cyclic voltammetry (CV) tests, and photodeposition techniques.
Assuntos
Norfloxacino , Processos Fotoquímicos , Norfloxacino/química , Catálise , OxirreduçãoRESUMO
In recent years, ionic covalent organic frameworks (iCOFs) have become popular for the removal of contaminants from water. Herein, we employed 2-hydroxybenzene-1,3,5-tricarbaldehyde (TFP) and 1,3-diaminoguanidine monohydrochloride (DgCl) to develop a novel leaf-like iCOF (TFP-DgCl) for the highly efficient and selective removal of non-steroidal anti-inflammatory drugs (NSAIDs). The uniformly distributed adsorption sites, suitable pore sizes, and functional groups (hydroxyl groups, guanidinium groups, and aromatic groups) of the TFP-DgCl endowed it with powerful and selective adsorption capacities for NSAIDs. Remarkably, the optimal leaf-like TFP-DgCl demonstrated an excellent maximum adsorption capacity (1100.08 mg/g) for diclofenac sodium (DCF), to the best of our knowledge, the largest adsorption capacity ever achieved for DCF. Further testing under varying environmental conditions such as pH, different types of anions, and multi-component systems confirmed the practical suitability of the TFP-DgCl. Moreover, the prepared TFP-DgCl exhibited exceptional reusability and stability through six adsorption-desorption cycles. Finally, the adsorption mechanisms of NSAIDs on leaf-like TFP-DgCl were confirmed as electrostatic interactions, hydrogen bonding, and π-π interactions. This work significantly supplements to our understanding of iCOFs and provides new insights into the removal of NSAIDs from wastewater.
Assuntos
Estruturas Metalorgânicas , Poluentes Químicos da Água , Adsorção , Anti-Inflamatórios não Esteroides , Diclofenaco , Águas Residuárias , Poluentes Químicos da Água/análiseRESUMO
BACKGROUND: Human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC) is a subtype of breast cancer with a worse prognosis. Little is known about the relationship between histology and prognosis among different distant metastasis sites (DMS). Our aims were to explore the prognostic value of histologic subtypes in different DMS and screen out specific subtypes with particular DMS that need more attention in HER2+ MBC. METHODS: HER2+ MBC patient data were obtained from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2014. Chi-squared tests were utilized to compare histologic subtypes in four DMS. The logistic regression analyses were used to control confounding factors. The log-rank tests were used to analyze the correlation of histologic subtype with disease-specific survival and overall survival. The survival data was analyzed using Kaplan-Meier methods. RESULTS: A total of 1174 HER2+ MBC patients were involved. First, the distribution of histological subtypes varied across metastatic sites, and the proportions of metastatic sites in different histological subtypes were also different. Furthermore, different histological subtypes within specific DMS showed divergent prognoses, and the different outcomes were shown by distinct DMS for specific histological subtypes. Among them, lobular carcinoma (ILC) subtypes showed the worst prognosis in bone metastasis, and lung metastasis predicted the worst prognosis in infiltration duct and lobular carcinoma (IDC-ILC) subtypes. After further consideration of hormone receptor (HR) status, the IDC-ILC subtype with liver metastasis in HR+/HER2+ MBC patients and the ILC subtype with bone metastasis in HR-/HER2+ MBC patients proved to be noteworthy. CONCLUSIONS: Histological subtypes are involved in determining the heterogeneity of HER2+ MBC patient prognosis, which is helpful to guide the prognosis prediction and monitoring of HER2+ breast cancer patients in clinics.
Assuntos
Neoplasias Ósseas , Neoplasias da Mama , Carcinoma Ductal de Mama , Carcinoma Lobular , Humanos , Feminino , Neoplasias da Mama/patologia , Estudos Retrospectivos , Carcinoma Lobular/patologia , Prognóstico , Carcinoma Ductal de Mama/patologia , Receptor ErbB-2/metabolismoRESUMO
Pulmonary fibrosis is a progressive and fatal fibrotic lung disease and associated with a high mortality rate. In the study, the prevention and treatment effects of fibroblast growth factor-21 (FGF-21) in bleomycin (BLM)-induced pulmonary fibrosis were investigated in vivo and vitro. In the prevention of pulmonary fibrosis studies, the results showed that interdict of FGF-21 could reduce the related gene and protein expression levels of pulmonary fibrosis. In addition, FGF-21 significantly reduced both the aggregation of inflammatory cells and deposition of collagen in the lung by histopathology. In therapy of pulmonary fibrosis studies, the results indicated that treatment with FGF-21 resulted in an amelioration of the pulmonary fibrosis in mice with reductions of the pathological score, collagen deposition and transforming growth factor (TGF)-ß and α-smooth muscle actin (α-SMA) expressions in the lung tissues at fibrotic stage, and late administration was also able to reduce the degree of pulmonary fibrosis and even better than these in the prevention group. Furthermore, BLM-induced THP-1 macrophage model was verified using FGF-21; the result showed that FGF-21 decreased the related gene expression level of pulmonary fibrosis. FGF-21 may have preventive and therapeutic effects on BLM-induced pulmonary fibrosis via inhibiting myofibroblast differentiation and inflammatory. Thus, FGF-21 represents a potential drug for the prevention and treatment of pulmonary fibrosis.
Assuntos
Fibrose Pulmonar , Camundongos , Animais , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/prevenção & controle , Bleomicina/efeitos adversos , Fibroblastos , Pulmão , Fatores de Crescimento de Fibroblastos/farmacologia , Fator de Crescimento Transformador beta/metabolismo , Fibrose , Colágeno/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Camundongos Endogâmicos C57BLRESUMO
Nitrate-driven anaerobic oxidation of methane (AOM), catalyzing by Candidatus Methanoperedens-like archaea, is a new addition in the global CH4 cycle. This AOM process acts as a novel pathway for CH4 emission reduction in freshwater aquatic ecosystems; however, its quantitative importance and regulatory factors in riverine ecosystems are nearly unknown. Here, we examined the spatio-temporal changes of the communities of Methanoperedens-like archaea and nitrate-driven AOM activity in sediment of Wuxijiang River, a mountainous river in China. These archaeal community composition varied significantly among reaches (upper, middle, and lower reaches) and between seasons (winter and summer), but their mcrA gene diversity showed no significant spatial or temporal variations. The copy numbers of Methanoperedens-like archaeal mcrA genes were 1.32 × 105-2.47 × 107 copies g-1 (dry weight), and the activity of nitrate-driven AOM was 0.25-1.73 nmol CH4 g-1 (dry weight) d-1, which could potentially reduce 10.3% of CH4 emissions from rivers. Significant spatio-temporal variations of mcrA gene abundance and nitrate-driven AOM activity were found. Both the gene abundance and activity increased significantly from upper to lower reaches in both seasons, and were significantly higher in sediment collected in summer than in winter. In addition, the variations of Methanoperedens-like archaeal communities and nitrate-driven AOM activity were largely impacted by the sediment temperature, NH4+ and organic carbon contents. Taken together, both time and space scales need to be considered for better evaluating the quantitative importance of nitrate-driven AOM in reducing CH4 emissions from riverine ecosystems.
Assuntos
Archaea , Nitratos , Archaea/genética , Archaea/metabolismo , Nitratos/metabolismo , Ecossistema , Rios , Metano/metabolismo , Anaerobiose , OxirreduçãoRESUMO
Chemoresistance is one of the major causes of therapeutic failure and poor prognosis for breast cancer patients, especially for triple-negative breast cancer patients. However, the underlying mechanism remains elusive. Here, we identified novel functional roles of heat shock protein beta-1 (HSPB1), regulating chemoresistance and ferroptotic cell death in breast cancer. Based on TCGA and GEO databases, HSPB1 expression was upregulated in breast cancer tissues and associated with poor prognosis of breast cancer patients, which was considered an independent prognostic factor for breast cancer. Functional assays revealed that HSPB1 could promote cancer growth and metastasis in vitro and in vivo. Furthermore, HSPB1 facilitated doxorubicin (DOX) resistance through protecting breast cancer cells from drug-induced ferroptosis. Mechanistically, HSPB1 could bind with Ikß-α and promote its ubiquitination-mediated degradation, leading to increased nuclear translocation and activation of NF-κB signaling. In addition, HSPB1 overexpression led to enhanced secretion of IL6, which further facilitated breast cancer progression. These findings revealed that HSPB1 upregulation might be a key driver to progression and chemoresistance through regulating ferroptosis in breast cancer while targeting HSPB1 could be an effective strategy against breast cancer.
Assuntos
Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , NF-kappa B/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Proteínas de Choque Térmico HSP27/genética , Proteínas de Choque Térmico HSP27/metabolismo , Resistencia a Medicamentos Antineoplásicos , Transdução de Sinais , Morte Celular , Linhagem Celular Tumoral , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Chaperonas Moleculares/metabolismoRESUMO
Breast cancer is the major common malignancy worldwide among women. Previous studies reported that cancer-associated fibroblasts (CAFs) showed pivotal roles in regulating tumor progression via exosome-mediated cellular communication. However, the detailed mechanism underlying the exosomal circRNA from CAFs in breast cancer progression remains ambiguous. Here, exosomal circRNA profiling of breast cancer-derived CAFs and normal fibroblasts (NFs) was detected by high-throughput sequencing, and upregulated circTBPL1 expression was identified in CAF exosomes. The exosomal circTBPL1 from CAFs could be transferred to breast cancer cells and promoted cell proliferation, migration, and invasion. Consistently, circTBPL1 knockdown in CAFs attenuated their tumor-promoting ability. Further exploration identified miR-653-5p as an inhibitory target of circTBPL1, and ectopic expression of miR-653-5p could partially reverse the malignant phenotypes induced by circTBPL1 overexpression in breast cancer. Additionally, TPBG was selected as a downstream target gene, and circTBPL1 could protect TPBG from miR-653-5p-mediated degradation, leading to enhanced breast cancer progression. Significantly, the accelerated tumor progression triggered by exosomal circTBPL1 from CAFs was confirmed in xenograft models. Taken together, these results revealed that exosomal circTBPL1 derived from CAFs contributed to cancer progression via miR-653-5p/TPBG pathway, indicating the potential of exosomal circTBPL1 as a biomarker and novel therapeutic target for breast cancer.
Assuntos
Neoplasias da Mama , Fibroblastos Associados a Câncer , Exossomos , MicroRNAs , Humanos , Feminino , Fibroblastos Associados a Câncer/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/metabolismo , Linhagem Celular Tumoral , Comunicação Celular , Neoplasias da Mama/patologia , Fibroblastos/metabolismo , Proliferação de Células/genética , Exossomos/metabolismo , Regulação Neoplásica da Expressão GênicaRESUMO
Small to mid-sized carnivores, or meso-carnivores, comprise a group of diverse mammals, many of which can adapt to anthropogenically disturbed environments. Wild meso-carnivores living in urban areas may get exposed to or spread pathogens to other species, including stray/feral domestic animals. Several coronaviruses (CoVs) have been detected in domesticated and farmed meso-carnivores, but knowledge of CoVs circulating in free-ranging wild meso-carnivores remains limited. In this study, we analyzed 321 samples collected between 2016 and 2022 from 9 species of free-ranging wild meso-carnivores and stray/feral domestic cats in the northeastern United States. Using a pan-CoV PCR, we screened tissues, feces, and saliva, nasal, and rectal swabs. We detected CoV RNA in fecal and saliva samples of animals in four species: fisher (Pekania pennanti), bobcat (Lynx rufus), red fox (Vulpes vulpes), and domestic cat (Felis catus). Next-generation sequencing revealed that all these viruses belonged to the Luchacovirus subgenus (Alphacoronavirus genus), previously reported only in rodents and lagomorphs (i.e., rabbits). Genetic comparison of the 3'-end of the genome (~12,000bp) revealed that although the viruses detected group with, and have a genetic organization similar to other luchacoviruses, they are genetically distinct from those from rodents and lagomorphs. Genetic characterization of the spike protein revealed that the meso-carnivore luchacoviruses do not have an S1/S2 cleavage motif but do have highly variable structural loops containing cleavage motifs similar to those identified in certain pathogenic CoVs. This study highlights the importance of characterizing the spike protein of CoVs in wild species for further targeted epidemiologic monitoring.
RESUMO
OBJECTIVE: Water buffalo, an important domestic animal in tropical and subtropical regions, play an important role in agricultural economy. It is an important source for milk, meat, horns, skin, and draft power, especially its rich milk that is the great source of cream, butter, yogurt, and many cheeses. In recent years, long noncoding RNAs (lncRNAs) have been reported to play pivotal roles in many biological processes. Previous studies for the mammary gland development of water buffalo mainly focus on protein coding genes. However, lncRNAs of water buffalo remain poorly understood, and the regulation relationship between mammary gland development/milk production traits and lncRNA expression is also unclear. METHODS: Here, we sequenced 22 samples of the milk somatic cells from three lactation stages and integrated the current annotation and identified 7,962 lncRNA genes. RESULTS: By comparing the lncRNA genes of the water buffalo in the early, peak, and late different lactation stages, we found that lncRNA gene lnc-bbug14207 displayed significantly different expression between early and late lactation stages. And lnc-bbug14207 may regulate neighboring milk fat globule-EGF factor 8 (MFG-E8) and hyaluronan and proteoglycan link protein 3 (HAPLN3) protein coding genes, which are vital for mammary gland development. CONCLUSION: This study provides the first genome-wide identification of water buffalo lncRNAs and unveils the potential lncRNAs that impact mammary gland development.
RESUMO
Photoreduction of CO2 to useful ingredients remains a great challenge due to the high energy barrier of CO2 activation and poor product selectivity. Herein, Polyvinyl pyrrolidone (PVP) coordinated BiOBr was synthesized by a facile chemical precipitation method at room temperature. The CO2 photoreduction behaviors of PVP coordinated BiOBr were evaluated with H2O without sacrificial agent under the simulated sunlight. The evolution rates of CO and CH4 are 263.2 µmol g-1h-1 and 3.3 µmol g-1h-1, which are 8 times and 2 times higher than those of pure BiOBr respectively. Furthermore, the coordination of PVP on BiOBr surface enhances greatly the selectivity of product CO, which is close to 100%. Loading PVP onto BiOBr could not only induce and stabilize the oxygen vacancy, but also increase the charge density of BiOBr via the ligand to metal charge transfer (LMCT), which could be beneficial to the adsorption and activation of CO2 molecule. The photoreduction mechanism of CO2 for PVP coordinated BiOBr was proposed based on the improved charge density of BiOBr by the experimental results and Density functional theory (DFT) calculations. This finding provides a new pathway to boost the conversion efficiency and selectivity for the activation of CO2 photoreduction and new molecule insights into the role of PVP in photocatalysis.